Abstract
Background
Proprotein convertase 5/6 (PC6) is critical for endometrial epithelial receptivity
and stromal cell decidualization for embryo implantation in women. We hypothesized
that inhibiting PC6 could block implantation for contraception. The aim of this study
was to prove this concept using human cell models and rabbits.
Study Design
A potential PC6 inhibitor, C1239-PEG-Poly R, was biochemically confirmed to be a potent
PC6 inhibitor. The potential contraceptive action of the inhibitor was then tested
in decidualization of primary human endometrial stromal cells in a human trophoblast
spheroid attachment model and in vivo in rabbits.
Results
The PC6 inhibitor C1239-PEG-Poly R inhibited in a dose-dependent manner both decidualization
and spheroid attachment. Vaginal delivery of 200 ��L of the inhibitor at a final concentration
of 5 mM to rabbits over a 3-day period starting 6 days after mating resulted in a
60% decrease in implantation and, hence, pregnancy.
Conclusions
This study presents proof of concept that PC6 inhibition has the potential to block
embryo implantation, providing nonhormonal contraception for women.
Keywords
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Article info
Publication history
Published online: November 14, 2011
Accepted:
October 5,
2011
Received in revised form:
October 4,
2011
Received:
September 13,
2011
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
